Bronchopulmonary dysplasia (BPD), a chronic lung disease of infancy epidemiologically associated with prematurity, hyaline membrane disease (HMD), mechanial ventilation (MV), and supplemental oxygen (O2), has become a major complicating sequela in surviving neonates. In pilot studies, 6/9 preterm baboons developed typical HMD (L/S ratio less than .8), confirmed pathologically in two. All required MV, supplemental O2 and supportive care identical to human infants. Three baboons maintained with 95-100% O2 for greater than 1 week developed clinical and pathological pictures consistent with BPD. Our results are consistent with the hypothesis that the primary lesion separating resolving HMD and BPD is a hyperplastic small airways lesion which can progress to an obliterative bronchiolitis that secondarily leads to distal alveolar atelectasis. The absence of pores of Kohn found in these and 14 control premature baboons suggests that minimal collateral ventilation may significantly contribute to this process. We hypothesize that BPD is the final result of the interactions of O2 toxicity and reparative processes in the immature lung in which MV has allowed survival. We plan to confirm the baboon model and investigate the contributions and interactions of O2 and MV in BPD by using high versus low inspired O2 and standard versus high frequency MV in four groups of animals. Evaluation of clinical and roentgenographic studies will be correlated with serial pulmonary function testing. Detailed morphologic and morphometric histology, along with biochemical analysis of the lung, will be performed at time of sacrifice. The results of this study should: 1) characterize a non-human primate model of BPD following HMD; 2) define measurable physiologic events that may precede the clinical recognition of BPD; 3) define the potential application and complications, both clinically and pathologically, which may be expected if high frequency ventilation is to be useed in human neonates; 4) direct future clinical studies toward either O2 toxicity or method of MV to minimize the occurrence of BPD; and 5) define the possibilities of survival with BPD in this model for long term correlative studies of pulmonary function and lung morphology.